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Clinical Color Vision Testing and Correlation

With Visual Function

JIAWEI ZHAO, SARITA B. DAVE, JIANGXIA WANG, AND PREM S. SUBRAMANIAN

 PURPOSE: To determine if Hardy-Rand-Rittler (H-R-R) complaints. Color vision testing also may be used to diag-
and Ishihara testing are accurate estimates of color vision in nose and follow progression of disease and monitor the
subjects with acquired visual dysfunction. onset of toxicity from some medications.15 Commonly
 DESIGN: Assessment of diagnostic tools. used and easily accessible color vision tests include the
 METHODS: Twenty-two subjects with optic neuropathy pseudoisochromatic plates, such as the Hardy-Rand-
(aged 1865) and 18 control subjects were recruited pro- Rittler (H-R-R) and Ishihara tests, and arrangement tests,
spectively from an outpatient clinic. Individuals with visual such as the Farnsworth-Munsell 100 and Farnsworth D-15
acuity (VA) <20/200 or with congenital color blindness hue discrimination test.
were excluded. All subjects underwent a comprehensive Pseudoisochromatic plate testing is inexpensive, readily
eye examination including VA, color vision, and contrast available, and quickly administered; therefore it is the test
sensitivity testing. Color vision was assessed using H-R-R of choice that clinicians use in the evaluation of their pa-
and Ishihara plates and Farnsworth D-15 (D-15) discs. tients with suspected or known optic neuropathy.5,6
D-15 is the accepted standard for detecting and classifying Pseudoisochromatic plates were originally developed to
color vision deficits. Contrast sensitivity was measured disclose the color confusion axes of congenital
using Pelli-Robson contrast sensitivity charts. dichromatism (protanopia, deuteranopia, and tritanopia)
 RESULTS: No relationship was found between H-R-R and function remarkably well at this task.6 Acquired pseu-
and D-15 scores (P [ .477). H-R-R score and contrast doisochromatic plate testing defects often do not respect
sensitivity were positively correlated (P [ .003). On multi- these confusion axes, and clinicians thus assign a score
variate analysis, contrast sensitivity (b [ 8.61, P < .001) reflecting the number of plates correctly identified. A prior
and VA (b [ 2.01, P [ .022) both showed association study showed that pseudoisochromatic plate identification
with H-R-R scores. Similar to H-R-R, Ishihara score did in patients with optic neuropathy was worse than expected
not correlate with D-15 score (P [ .973), but on multivar- from visual acuity (VA) loss alone,5 while another showed
iate analysis was related to contrast sensitivity (b [ 8.69, that pseudoisochromatic plate test performance declined in
P < .001). H-R-R and Ishihara scores had an equivalent concert with reduced visual acuity and/or visual field loss of
relationship with contrast sensitivity (P [ .069). any etiology.7
 CONCLUSION: Neither H-R-R nor Ishihara testing Arrangement tests require patients to sort colored caps
appears to assess color identification in patients with optic of fixed chroma into a sequence or into groups. These tests
neuropathy. Both H-R-R and Ishihara testing are are designed without assuming that colors are confused
correlated with contrast sensitivity, and these tests may owing to congenital color vision loss, allowing errors to
be useful clinical surrogates for contrast sensitivity be made across the color circle and between adjacent
testing. (Am J Ophthalmol 2015;160(3):547552. hues.15,8 Moreover, in contrast to pseudoisochromatic
2015 by Elsevier Inc. All rights reserved.) plate testing, arrangement tests allow quantification of
severity of disease and may be more sensitive in
detecting early visual dysfunction.5,6,9 Arrangement

C
OLOR VISION TESTING IS A ROUTINE PART OF THE tests have been demonstrated to be very effective in
neuro-ophthalmologic examination and often is following and classifying acquired color defects,4,6,10 but
used by comprehensive ophthalmologists to screen their use has been limited owing to their time-
for suspected optic neuropathy in patients with new visual consuming nature.5,11
Clinicians often use abnormal pseudoisochromatic
plate testing results as evidence for optic neuropathy,
Supplemental Material available at AJO.com. and standard clinical teaching reinforces this idea.12
Accepted for publication Jun 16, 2015. While patients with optic neuropathy5,13 and retinal
From the Wilmer Eye Institute, The Johns Hopkins University School
of Medicine, Baltimore, Maryland. dystrophy14 often have decreased pseudoisochromatic
Prem S. Subramanian is now at the University of Colorado School of plate test scores, we have observed that patients with
Medicine, Department of Ophthalmology, Aurora, Colorado. other conditions such as dry eye syndrome also can
Inquiries to Prem S. Subramanian, Department of Ophthalmology,
University of Colorado School of Medicine, 1675 Aurora Ct, Aurora, have abnormal pseudoisochromatic plate test scores.
CO 80045; e-mail: prem.subramanian@ucdenver.edu We sought to determine if poor scores on H-R-R and

0002-9394/$36.00 2015 BY ELSEVIER INC. ALL RIGHTS RESERVED. 547


http://dx.doi.org/10.1016/j.ajo.2015.06.015
TABLE 1. Demographic Data of Patients With Optic TABLE 2. Comparison of Visual Function, Including Color
Neuropathy and Normal Controls Vision Testing, Between Affected Eyes of Patients and
Control Eyes
Patients Controls
(N 22) (N 18) P Valuea Patient Eyes Control Eyes
Test Result (N 31) (N 36) P > jzj
Mean age in years (SD) 48.0 (10.54) 41.3 (11.5) .067
Sex, N (%) .51 H-R-R score (# of plates 19.1 (1.7) 20.0 (0.1) .019
Female 13 (61.5) 13 (72.2) correct)a
Male 9 (38.5) 5 (27.8) Ishihara score (# of plates 15.1 (2.0) 16.0 (0) .043
Ethnicity, N (%) .184 correct)a
White 16 (72.7) 9 (50) D-15 score [15  (number of 14.6 (0.8) 15.0 (0) .040
Black 4 (18.2) 8 (44.4) errors)]a
Asian 1 (.5) 1 (5.6) Contrast sensitivity 1.5 (0.2) 1.7 (0.04) .003
Hispanic 1 (.5) 0 (0) (log units)a
VA (logMAR) 0.06 (0.2) 0.033 (0.1) .288
a
P values determined by Fisher exact test for sex and ethnicity
and t test for age. H-R-R Hardy-Rand-Rittler; VA visual acuity.
Both eyes of control subjects and the affected eye(s) of pa-
tients are included. Mean and standard deviation of each test
result are listed. Linear mixed-effects regression models with a
Ishihara plate testing represent truly aberrant color vision random intercept for patients were used to compare the 2
or indicate a decrement of other psychovisual parameters. groups. All measures of visual function were reduced in the
We hypothesized that reduced pseudoisochromatic plate affected eyes relative to the control eyes, except for visual acuity.
a
test scores would correlate with contrast sensitivity loss Test with results that are significantly different between pa-
and not reflect true color vision defects as determined tient and control eyes at a 0.05.
by color arrangement testing.

the Farnsworth D-15 test (PV-16 Quantitative color


vision test; Precision Vision, Lasalle, Illinois, USA).
METHODS The affected eye or eyes of patients and both eyes of con-
trol subjects were tested.
 SUBJECTS: This study was a prospective clinical investi- Pseudoisochromatic plate testing was done under stan-
gation. All study procedures were approved in advance of dardized lighting (basic fluorescent 30 watt bulb) and the
the study by the Institutional Review Board of the Johns plates were held 30 cm away from the patient at a perpen-
Hopkins University School of Medicine and adhered to dicular angle to the line of sight. The score for the Ishi-
the requirements of the Health Insurance Portability and hara test was set as the number of plates identified out
Accountability Act. Informed consent was obtained from of the first 15 screening plates. Scoring followed a stan-
all subjects. Study subjects between ages 18 and 65 were dard clinical rubric. For the 1-digit plate, subjects were
recruited prospectively from the Wilmer Eye Institute at awarded 1 point for correctly identifying the shown num-
the Johns Hopkins Hospital. Patients with acquired optic ber and 0 points for not seeing or incorrect identification.
neuropathy (glaucoma, ischemic optic neuropathy, optic For the 2-digit plate, subjects were awarded 1 point for
neuritis, or compressive optic neuropathy) (n 22) were correctly identifying both numbers on the plate, half a
included. Control subjects (n 18) had no ocular pathol- point for identifying 1 number, and 0 points for not seeing
ogy other than corrected refractive error and had no known or incorrect identification of both numbers. The score for
neurological disease. the H-R-R test was set as the number of plates identified
Individuals with best-corrected VA <20/200 at distance out of the 20 screening and diagnostic plates (numbers
or near equivalent or with congenital color vision deficits 5-24). For plates containing 1 shape, subjects received 1
were excluded (patients and controls). All subjects under- point for correctly identifying the figure and 0 points for
went a comprehensive eye examination, including assess- not seeing or incorrect identification. For plates contain-
ment of best-corrected Snellen acuity, pupillary response, ing 2 shapes, subjects received 1 point for correctly iden-
and funduscopy. tifying both figures, half a point for identifying 1 shape,
and 0 points for not seeing or incorrect identification of
 COLOR VISION TESTING: Monocular color vision both shapes. The Farnsworth D-15 test consists of 15
testing was done with H-R-R pseudoisochromatic plates colored discs comprising the entire color spectrum. Un-
(4th edition; Richmond Products Inc, Albuquerque, der simulated natural daylight conditions (OttLite 508
New Mexico, USA), Ishihara pseudoisochromatic plates illumination, Tampa, Florida), subjects were asked to
(1997 version; Kanehara & Co, Ltd, Tokyo, Japan), and arrange the discs in order, according to the color, on a

548 AMERICAN JOURNAL OF OPHTHALMOLOGY SEPTEMBER 2015


FIGURE 1. Evaluation of potential correlation between Hardy-Rand-Rittler scores and other clinical tests of visual function. Data
from 31 eyes (22 patients) with optic neuropathy are shown. Scatterplots show Hardy-Rand-Rittler (H-R-R) scores on the y-axis
with Farnsworth D-15 score or contrast sensitivity on the x-axis. (Left) No significant correlation found between H-R-R score
and Farnsworth D-15 score (Kendall correlation [ 0.058, P [ .477). (Right) Correlation is seen between H-R-R score and contrast
sensitivity (Kendall correlation [ 0.314, P [ .003).

statistical association of nonparametric data pairs, was


TABLE 3. Multivariate Analysis of Contrast Sensitivity, Visual used to measure the correlations between the following
Acuity, Age, and Farnsworth D-15 and Their Association With pairs of variables in affected patient eyes: H-R-R score
Hardy-Rand-Rittler Test Scores in the 31 Eyes of Optic
and contrast sensitivity, H-R-R score and Farnsworth D-
Neuropathy Patients
15 score, Ishihara score and contrast sensitivity, and Ishi-
Coefficient 95% Confidence hara score and Farnsworth D-15 score. A multivariate
Variable (Beta) Interval P > jzj linear mixed-effects model also was employed to deter-
Contrast 8.611a 6.94310.279 <.001 mine the association of contrast sensitivity with H-R-R
sensitivity and Ishihara score in affected patient eyes; fixed effects
Visual acuity 1.486 0.1813.153 .081 included contrast sensitivity, visual acuity, age, and Farns-
Age 0.026 0.0120.064 .172 worth D-15 score. A random intercept for patients was
D-15 0.274 0.5630.015 .063 used to account for the correlation between the right
a
and left eyes from the same patient. Statistical analysis
indicates coefficient that is significant at a 0.05.
was performed using Stata 12.1 (StataCorp LP, College
Station, Texas, USA). A P value of < _.05 was considered
statistically significant.
black-colored surface. One point was deducted from a
maximum score of 15 for each misplaced disc.

 CONTRAST SENSITIVITY TESTING: Contrast sensitivity RESULTS


was assessed monocularly and binocularly using the Pelli-
Robson contrast sensitivity charts at 1 m. The same light- TWENTY-TWO ELIGIBLE PATIENTS WERE IDENTIFIED, OF
ing apparatus used in pseudoisochromatic plate testing was whom 9 had bilateral disease. Six had optic neuritis, 5
employed to uniformly illuminate the charts. The faintest had nonarteritic anterior ischemic optic neuropathy
triplet for which at least 2 of the 3 letters were correctly (NAION), 8 had compressive optic neuropathy, 1 had
identified indicated the log contrast sensitivity score of glaucoma, 1 had idiopathic noncompressive optic neurop-
the tested eye(s). athy, and 1 had optic nerve hypoplasia. Eighteen subjects
with no ocular pathology other than corrected refractive
 STATISTICS: Descriptive statistics (Fisher exact for error were identified as controls. Demographic data for pa-
ethnicity and sex and t test for age) were used to compare tients and controls are shown in Table 1. Comparison of vi-
demographic data between the patients and controls. To sual function between affected patient eyes and control
account for the correlation between left and right eyes eyes is presented in Table 2. Patients with bilateral disease
from the same subject, linear mixed-effects regression had both eyes tested, giving a total of 31 eyes, and both eyes
models with a random intercept for patients were used (n 36) of control subjects were included in all analyses.
to test the difference between patient and control eyes Contrast sensitivity, H-R-R score, Ishihara score, and D-
in terms of tests results from H-R-R, Ishihara, and D-15; 15 score were significantly reduced in affected eyes
contrast sensitivity; and visual acuity. The Kendall compared to control eyes, although Snellen visual acuity
tau correlation coefficient, which is used to determine was not (Table 2).

VOL. 160, NO. 3 COLOR VISION TESTING AND CONTRAST SENSITIVITY 549
FIGURE 2. Evaluation of potential correlation between Ishihara scores and other clinical tests of visual function. Data from 31 eyes
(22 patients) with optic neuropathy are shown. Scatterplots display Ishihara scores on the y-axis and Farnsworth D-15 score or
contrast sensitivity on the x-axis. (Left) No correlation found between Ishihara score and D-15 score (Kendall correlation [
0.002, P [ 1.0). (Right) Correlation between Ishihara score and contrast sensitivity did not reach statistical significance in this
analysis (Kendall correlation [ 0.148, P [ .055).

correlation between contrast sensitivity and the Ishihara


TABLE 4. Multivariate Analysis of Contrast Sensitivity, Visual score was found (Kendall coefficient 0.148, P .055)
Acuity, Visual Field Deficit, Age, and Farnsworth D-15 and in this pairwise analysis (Figure 2). However, contrast
Their Association With Ishihara Test Scores in the 31 Eyes of
sensitivity was associated with the Ishihara score (P <
Optic Neuropathy Patients
.001) when multivariate analysis was performed
Coefficient 95% Confidence (Table 4). Additionally, this multivariate analysis showed
Variable (Beta) Interval P > jzj that age was associated with Ishihara score (P .014). Vi-
Contrast sensitivity 6.869 a
3.73410.003 <.001 sual acuity (P .367) and Farnsworth D-15 score (P
Visual acuity 1.542 1.8124.895 .367 .254) were not associated with the Ishihara score in the
Age 0.072a 0.0140.128 .014 multivariate analysis, showing that no relationship exists
D-15 0.376 1.0210.270 .254 between color identification on the Farnsworth D-15 test
a
and the number of Ishihara plates correctly recognized
indicates coefficient that is significant at a 0.05. (Supplemental Tables 1-3, available online at AJO.com).

 COMPARISON OF HARDY-RAND-RITTLER AND ISHI-


 ANALYSIS OF HARDY-RAND-RITTLER TEST: Using the HARA TESTS: Comparison of the Kendall correlation coef-
Kendall correlation (Figure 1), we found no correlation be- ficients of H-R-R score and contrast sensitivity to Ishihara
tween H-R-R score and Farnsworth D-15 score (Kendall score and contrast sensitivity showed that neither test had a
coefficient 0.058, P .477) in the affected eye(s) of pa- stronger correlation with contrast sensitivity than the other
tients; however, H-R-R score and contrast sensitivity had a (P .069).
positive correlation (Kendall coefficient 0.314, P
.003), indicating that a decrease in contrast sensitivity
threshold was associated with poorer H-R-R plate identifi- DISCUSSION
cation. Multivariate analysis (Table 3) was employed to
evaluate potential effects of other variables such age and PATIENTS WITH A VARIETY OF OPTIC NERVE DISORDERS WERE
visual acuity. We found that only contrast sensitivity found to have abnormal performance on pseudoisochromatic
threshold was significantly associated with H-R-R scores plate testing. We have shown that neither H-R-R nor
(P < .001), while age, visual acuity, and Farnsworth D-15 Ishihara plates appear to assess true color recognition based
scores were not (P .172, P .081, and P .063, respec- on comparison of pseudoisochromatic plate testing with
tively). Thus, accuracy of color identification on the Farns- D-15 testing. Instead, they both appear to correlate with
worth D-15 test did not show a significant relationship with contrast sensitivity on multivariate analysis, although only
the number of H-R-R plates identified correctly. H-R-R score correlated with contrast sensitivity on pairwise
analysis using the Kendall coefficient. Neither H-R-R nor
 ANALYSIS OF ISHIHARA TEST: Similar to findings on Ishihara scores were decreased as a function of visual acuity
H-R-R testing, no correlation was found between Ishihara in multivariate analysis, which stands in contrast to a previ-
score and Farnsworth D-15 score in the affected eye(s) of ous study in which H-R-R, Ishihara, and D-15 scores declined
patients (Kendall coefficient 0.002, P .973) using with experimental reduction (by fogging) of visual acuity in
the Kendall correlation. Additionally, no significant normal subjects.7 In the current study, Ishihara score, but not

550 AMERICAN JOURNAL OF OPHTHALMOLOGY SEPTEMBER 2015


H-R-R, was reduced with age in affected eyes of patients with lighting, reflections, and fading of the charts.22 We propose
optic neuropathy. that H-R-R or Ishihara testing may be used as an alternative
H-R-R and Ishihara plates have colored dots of variable means of detecting reduced contrast sensitivity in patients
size, hue, and saturation that are arranged into simple with optic neuropathy, based on our findings.
shapes or numbers in a background of similar dots. Pseudoi- Limitations of our study include the relatively small sam-
sochromatic plates have been reported to have luminous ple sizes of patients and controls, the limited variety of op-
reflectance differences between the figure and back- tic nerve diseases, and the selection of Farnsworth D-15 test
ground.15 Such differences alter color perception16 and as our standard color vision test vs Farnsworth-Munsell
can reduce color figure detection against a gray background 100. Farnsworth-Munsell 100 is more sensitive in the
as luminance is changed.17 This design strategy is very detection of acquired color vision deficiency23 but requires
effective for detecting congenital color vision defects by prolonged concentration of the patients and may have a
hiding the figures in a background but may introduce un- higher number of false-positive results.11 We examined
wanted contrast-related elements. patients with optic neuropathy and cannot extend our find-
A prior study showed that H-R-R is more sensitive than ings to patients with other causes of vision disturbance. We
Ishihara testing in identifying patients with optic neuropa- did evaluate a patient with dry eye syndrome and 3 patients
thies.13 Although only H-R-R results had a significant corre- with retinal dystrophy and obtained similar findings (data
lation with contrast sensitivity in pairwise testing, the not shown). Therefore, we are currently studying a larger
multivariate analysis showed both H-R-R and Ishihara tests cohort of patients with dry eye, which reduces contrast
to have a strong correlation with contrast sensitivity and no sensitivity,24 in order to expand upon our observations.
significant difference between them in this regard. Reduced In conclusion, this study was intended to explore if
contrast sensitivity has been described in the majority of pa- apparent color vision deficits measured by H-R-R and Ishi-
tients with demyelinating disease even in the absence of clin- hara tests represent true color vision impairment or indi-
ical optic neuropathy.18 Poor contrast sensitivity may precede cate reduction in other psychovisual parameters, such as
the onset of optic neuropathy in thyroid eye disease patients as contrast sensitivity or visual acuity. Our findings show
well.19 Low-contrast vision testing may tell the examiner that H-R-R or Ishihara tests may be used as inexpensive
more about the function of the parvocellular retinal ganglion and readily available surrogate measures of contrast sensi-
cells, which sustain damage in compressive and demyelin- tivity. Pseudoisochromatic plate tests were designed to
ating optic neuropathies.20,21 Measuring contrast sensitivity identify congenital color vision deficits, and clinicians
in the clinical setting is hampered by time constraints and should not rely upon them to identify patients with ac-
poor reliability or variability in test results owing to quired color vision abnormalities.

ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST.
Financial Disclosures: J.W.: NEI, grant support; P.S.S.: NEI, grant support; US Department of Defense, grant support; Stryker Corp (Kalamazoo, Michi-
gan), grant support; Novartis AG (Basel, Switzerland), grant support; National Aeronautics and Space Administration, consultant; Wolters Kluwer (Balti-
more, Maryland), royalties; CME Solutions, Inc (Tucson, Arizona), payment for educational material development, travel expenses for meeting
presentations; various law firms, expert witness testimony. Funding/Support: Supported in part by an unrestricted grant to the Wilmer Eye Institute
from Research to Prevent Blindness, USA and Wilmer Biostatistics Core Grant EY01765. All authors attest that they meet the current ICMJE require-
ments to qualify as authors.

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552 AMERICAN JOURNAL OF OPHTHALMOLOGY SEPTEMBER 2015


SUPPLEMENTAL TABLE 1. Relationship Between SUPPLEMENTAL TABLE 3. Comparison of Visual Function
Farnsworth D-15 and Hardy-Rand Rittler When Considering Between Patients With Optic Neuropathy and Normal
Contrast Sensitivity in Patients With Optic Neuropathy Farnsworth D-15 but Abnormal Hardy-Rand-Rittler or
Ishihara Results, and Patients With Optic Neuropathy and
Variable Coefficient (Beta) P > jzj Normal Hardy-Rand-Rittler or Ishihara but Abnormal D-15
a
Results
HRR 0.244 .023
Contrast sensitivity 2.266a .019 Normal D-15, Abnormal D-15,
Abnormal Normal PIP
HRR Hardy-Rand Rittler. Visual Function PIP (n 10) (n 6) P > jzj
a
Indicates coefficient that is significant at a < 0.05.
Contrast sensitivity 1.65 (0.91.65) 1.65 (1.51.65) .532
(log units)
VA (logMAR) 0 (0.10.3) 0 (0.10) .567

PIP pseudoisochromatic plates; VA visual acuity.


SUPPLEMENTAL TABLE 2. Relationship Between
Wilcoxon rank sum test was used to compare the 2 groups.
Farnsworth D-15 and Ishihara Plate Testing, Accounting for
Median and range of each test result are shown.
Contrast Sensitivity, in Patients With Optic Neuropathy

Variable Coefficient (Beta) P > jzj

Ishihara 0.12 .092


Contrast sensitivity 1.22 .089

VOL. 160, NO. 3 COLOR VISION TESTING AND CONTRAST SENSITIVITY 552.e1
Reproduced with permission of the copyright owner. Further reproduction prohibited without
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